Recent papers (selected)Serine-129 phosphorylation of α-synuclein is an activity-dependent trigger for physiologic protein-protein interactions and synaptic function. Parra-Rivas and Madhivanan et al., Neuron Dec 2023. See Cover.
Synapsin E-domain is essential for α-synuclein function. Stavsky A et al., eLife May 2024 Clathrin packets move in slow axonal transport and deliver functional payloads to synapses. Ganguly A, and Sharma R et al. Neuron, Sept 2021. Gene-based therapies for neurodegenerative diseases (review). Sun and Roy, Nature Neuroscience, Feb 2021 Functional cooperation of α-synuclein and VAMP2 in synaptic vesicle recycling. Sun et al., PNAS, May 2019 Synapsins regulate α-synuclein function. Atias et al., PNAS, May 2019 CRISPR/Cas9 editing of APP C-terminus attenuates β-cleavage and promotes α-cleavage. Sun et al., Nature Communications, Jan 2019 Processive flow by biased polymerization mediates the slow axonal transport of actin. Chakrabarty et al., Journal of Cell Biology, Jan 2019 The physical approximation of APP and BACE-1: A key event in Alzheimer's disease pathogenesis. Sun J and Roy S. Developmental Neurobiology, Mar 2018 The Nano-Architecture of the Axonal Cytoskeleton. Leterrier C, Dubey P and Roy S. Nature Reviews in Neuroscience , Dec 2017 Hsc70 chaperone activity is required for the cytosolic slow axonal transport of synapsin. Ganguly et al., Journal of Cell Biology. July 2017 Visualization of APP and BACE-1 approximation in neurons: new insights into the amyloidogenic pathway. Das et al., Nature Neuroscience, Jan 2016 A dynamic formin-dependent deep F-actin network in axons. Ganguly et al., Journal of Cell Biology, Aug 2015 α-Synuclein Multimers Cluster Synaptic Vesicles and Attenuate Recycling. Wang et al., Current Biology, Oct 2014 Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway. Das et al., Neuron, Aug 2013 Fast vesicle transport is required for the slow axonal transport of synapsin. Tang et al., Journal of Neuroscience, Sept 2013 |
Neuronal Trafficking and CRISPR therapeutics
"The science of living things is the science of movement and transformation" - Leonardo Da Vinci, 1452-1519
A static cell is a dead cell, and life depends on precise spatiotemporal trafficking of molecules. This is especially true for neurons, where the vast majority of proteins are synthesized in small cell-bodies and transported into elaborate axons and synapses. Movement within micron-sized synapses is also vital, and it is clear that trafficking of molecules – rather than their mere presence – is a critical determinant of synaptic function. Understanding trafficking pathways often gives insight into disease mechanisms, offering clues into early events that can be therapeutically manipulated. For instance, trafficking of APP (amyloid precursor protein) into various cellular compartments dictates its proteolytic cleavage, and consequent production of pathologic amyloid-beta fragments in Alzheimer’s disease. Similarly, alpha-synuclein – a protein involved in Parkinson’s disease – is important in regulating the trafficking of synaptic vesicles. Projects in the lab are centered around understanding the cell biology of neuronal trafficking in physiology and disease. Translational projects use gene-editing to manipulate trafficking-pathways in Alzheimer’s and Parkinson’s disease to help advance next-generation neurotherapeutics for these devastating illnesses. |
Recent HighlightsMay 2025: Undergrad Arnav awarded research scholarship: https://bsky.app/profile/roylab-ucsd.bsky.social/post/3loqn7loyx22
April 2025: Patrick Kearney awarded NIA T32 fellowship. Dec 2024: Tamara's Lrrk2 abstract selected for a talk at ASCB 2024. Oct 2024: Welcome Arnav Godavarthi, new undergrad in the lab. June 2024: News story of our Alzheimer's CRISPR strategy in Alzforum Link June 2024: BioRxiv preprint on gene editing in Alzheimer's Link June 2024: BioRxiv preprint on role of phase separation in development of axonal periodic structure Link May 2024: New publication finalized in eLife. March 2024: New postdoc Anshul joins the lab. March 2024: "Spotlight" on our alpha-synuclein phosphorylation paper by Danielle Mor (Augusta U): Link to paper Feb 2024: Podcast in journal Neurology on functional role of serine-129 alpha-synuclein phosphorylation: Link to Podcast Jan 2024: NIH news story on our recent work on alpha-synuclein phosphorylation. Dec 2023: New cover article on alpha-synuclein Ser129 phosphorylation in Neuron. Dec 2023: Subhojit interviewed in Nature on developing CRISPR therapies for Alzheimer's disease: https://www.nature.com/articles/d41586-023-03931-5 Sept 2023: Welcome Yiqin Shen, who joins the lab as a research assistant. Aug 2023: New paper in eLife. Aug 2023: Welcome Marissa, new undergraduate student. July 2023: Brent receives postdoctoral fellowship from the Alzheimer's association. July 2023: Lab receives Alzheimer's disease research award from the BrightFocus Foundation. July 2023: Brent and Leo present at AAIC, Amsterdam. News stories on Brent's Alzheimer's gene-editing work was highlighted in: - Stat News - Fierce Biotech - Neurology Today July 2023: Leo received the Launch Award (mentored training and transition) from the Parkinson's Foundation! Link June 2023: Welcome Neda, new Research Assistant in the lab! April 2023: New postdoc in the lab. Welcome Alec! Oct 2022: New postdoc in the lab. Welcome Sheila! July 2022: New postdoc in the lab. Welcome Patrick! Mar 2022: Rohan's new baby in lab alert. Feb 2022 - Our review on gene therapy and gene editing for neurodegeneration highlighted in Nature collections: https://www.nature.com/collections/ajadgefeih Jan 2022 - Transformative $50M gift to UCSD and USC will support Alzheimer's research, including potential CRISPR therapies pursued by our lab. UCSD press release: https://ucsdnews.ucsd.edu/pressrelease/with-a-50-million-gift-usc-and-uc-san-diego-join-forces-in-alzheimers-research Dec 2021 - We welcome two new postdocs - Veronica and Tamara. Oct 2021 - New collaborative grant from ASAP, led by V. Gradinaru at Caltech: https://www.caltech.edu/about/news/caltech-researchers-team-up-to-fight-parkinsons-disease Sept 2021 - Our "clathrin packet" paper highlighted in Nature Reviews in Neuroscience "Delivering Clathrin": https://www.nature.com/articles/s41583-021-00529-6 Sept 2021 - New paper on clathrin: https://www.cell.com/neuron/fulltext/S0896-6273(21)00613-9www.cell.com/neuron/fulltext/S0896-6273(21)00613-9 July 2021 - Archan and Rohan et al. paper on clathrin transport and synaptic targeting accepted in Neuron. July 2021 - Lab awarded a Foundation grant to work on CRISPR therapies for Parkinson's disease. July 2021 - Leo awarded a postdoctoral fellowship from the American Parkinson's Disease Association (APDA). June 2021 - Nihal Satyadev (medical student) joins lab as part of NIA-funded Medical Student Training in Aging Research (MSTAR) scholarship program May 2021 - Subhojit presents Brent APP-editing work at the SCGE (Somatic Cell Genome Editing) consortium annual meeting. April 2021 - Perspective on SCGE (Somatic Cell Genome Editing) published in Nature: https://www.nature.com/articles/s41586-021-03191-1 March 2021 - Subhojit presents Archan and Rohan's clathrin work at the annual German Neuroscience Society meeting. Feb 2021 - Jichao and Subhojit's review on gene therapy and neurodegeneration published in Nature Neuroscience: https://www.nature.com/articles/s41593-020-00778-1 Jan 2021 -Brent awarded a postdoctoral training fellowship on Alzheimer's disease (T32). |
